US7461968B2 - System, device, and method for mixing liquids - Google Patents

Abstract

A system, device, and method for mixing liquids involves pumping a first liquid into a first pump chamber of a pumping apparatus through a channel of the pumping apparatus and pumping a second liquid from a second pump chamber of the pumping apparatus into either the channel or the first pump chamber, preferably while the first liquid is being pumped into the first pump chamber, so that the two liquids are mixed within the pumping apparatus. The second liquid is preferably pumped in a pulsatile mode in which small quantities of the second liquid are pumped at intervals. The quantity and/or the interval can be dynamically adjusted to result in a predetermined concentration of the two liquids. The contents of the first pump chamber are pumped to a receptacle.

Description

CROSS-REFERENCE TO RELATED APPLICATION(S)

The present application may include subject matter related to one or more of the following commonly-owned United States patent applications, each of which was filed on even date herewith and is hereby incorporated herein by reference in its entirety: U.S. patent application Ser. No. 10/696,969 entitled SYSTEM, DEVICE, AND METHOD FOR MIXING A SUBSTANCE WITH A LIQUID (referred to herein as “Application D70”); U.S. patent application Ser. No. 10/696,818, now U.S. Pat. No. 7,086,700 entitled TWO-STAGE MIXING SYSTEM, APPARATUS, AND METHOD (referred to herein as “Application D72”); U.S. patent application Ser. No. 10/697,176 entitled SYSTEM AND METHOD FOR PUMPING FLUID USING A PUMP CASSETE (referred to herein as “Application D73”); U.S. patent application Ser. No. 10/696,984 entitled DOOR LOCKING MECHANISM (referred to herein as “Application D74”); U.S. patent application Ser. No. 10/697,450 entitled BEZEL ASSEMBLY FOR PNEUMATIC CONTROL (referred to herein as “Application D75”); U.S. patent application Ser. No. 10/697,862 entitled PUMP CASSETE WITH SPIKING ASSEMBLY (referred to herein as “Application D84”); and U.S. patent application Ser. No. 10/696,990 entitled PUMP CASSETTE BANK (referred to herein as “Application D85”).

FIELD OF THE INVENTION

The present invention relates generally to pumping liquids, and more particularly to a system, device, and method for mixing liquids.

BACKGROUND OF THE INVENTION

Millions of people receive blood transfusions each year. Although helpful in many cases, blood transfusions have associated risks. Among others, there is a risk that microorganisms capable of causing disease (i.e., pathogens) could pass from the donor blood to the ultimate blood recipient. For example, untreated blood used in a blood transfusion could have pathogens causing the West Nile Virus, or AIDS. It thus is critical for the public health to ensure that transfused blood is substantially free of pathogens.

The medical community has responded to this need by developing various techniques for removing known and unknown pathogens from donated blood. One technique involves mixing precise amounts of a diluted anti-pathogen compound with blood. Some time after mixing, a rinsing process removes the anti-pathogen compound from the blood. One complexity with this process, however, is the fact that the diluted anti-pathogen compound has a very short shelf life (e.g., on the order of about four hours). Accordingly, the diluted anti-pathogen compound must be produced a relatively short time before it is mixed with blood.

The anti-pathogen compound is not easy to handle before it is diluted. To the contrary, it has a very high pH (e.g., on the order of 11.0 or higher) and thus, is highly caustic and toxic. Mere contact with the undiluted solution can melt plastic, or burn flesh. Because of these undesirable properties, the undiluted solution typically is manually diluted by highly trained laboratory technicians that necessarily must be protected from direct contact with it. Consequently, laboratory technicians often are required to wear relatively impermeable protective gear while diluting the solution behind a chemical laminar flowhood. Such a process, however, is inherently slow, imprecise, and costly due to the multitude of safety requirements. Moreover, even with safeguards, diluting the undiluted solution still poses a risk to the laboratory technician.

SUMMARY OF THE INVENTION

In accordance with one aspect of the invention, mixing liquids involves pumping a first liquid into a first pump chamber of a pumping apparatus through a channel of the pumping apparatus and pumping a second liquid from a second pump chamber of the pumping apparatus into either the channel or the first pump chamber, preferably while the first liquid is being pumped into the first pump chamber, so that the two liquids are mixed within the pumping apparatus. The second liquid is preferably pumped in a pulsatile mode in which small quantities of the second liquid are pumped at intervals. The quantity and/or the interval can be dynamically adjusted to result in a predetermined concentration of the two liquids. The contents of the first pump chamber are pumped to a receptacle.

In accordance with another aspect of the invention, a method for mixing a first liquid with a second liquid involves pumping a first liquid into a first pump chamber of a pumping apparatus through a channel of the pumping apparatus and pumping a quantity of a second liquid from a second pump chamber of the pumping apparatus into one of the channel and the first pump chamber so as to mix the first liquid and the second liquid within the pumping apparatus. The quantity of the second liquid is preferably pumped during the pumping of the first liquid. The pumping apparatus may be a pneumatically operated pump cassette having various pneumatically operated pump chambers and valves. The second liquid may be pumped in a pulsatile mode. The pulse width and pulse interval may be dynamically adjusted to obtain a predetermined concentration of first liquid and second liquid. The contents of the first pump chamber may be pumped to a receptacle.

In accordance with another aspect of the present invention, an apparatus for mixing a first liquid with a second liquid includes a first pump controller operatively coupled to pump a first liquid into a first pump chamber of a pumping apparatus through a channel of the pumping apparatus and a second pump controller operatively coupled to pump a quantity of a second liquid from a second pump chamber of the pumping apparatus into one of the channel and the first pump chamber so as to mix the first liquid and the second liquid within the pumping apparatus. The quantity of the second liquid is preferably pumped during the pumping of the first liquid. The pumping apparatus may be a pneumatically operated pump cassette having various pneumatically operated pump chambers and valves. The second liquid may be pumped in a pulsatile mode. The pulse width and pulse interval may be dynamically adjusted to obtain a predetermined concentration of first liquid and second liquid. The contents of the first pump chamber may be pumped to a receptacle. The apparatus may include a pump cassette interface for pneumatically operating the chambers and valves of the pump cassette. The pump cassette interface may include a limiter for limiting the amount of second liquid held by the second pump chamber.

In accordance with another aspect of the present invention, an apparatus for mixing a first liquid with a second liquid includes means for pumping a first liquid into a first pump chamber of a pumping apparatus through a channel of the pumping apparatus and means for pumping a quantity of a second liquid from a second pump chamber of the pumping apparatus into one of the channel and the first pump chamber so as to mix the first liquid and the second liquid within the pumping apparatus.

In accordance with another aspect of the present invention, a system for mixing a first liquid with a second liquid includes a plurality of first liquid containers, each containing a first liquid; a second liquid container containing a second liquid; and a plurality of pumps, each pump operatively coupled to mix first liquid from a respective one of the plurality of first liquid containers with second liquid from the second liquid container. The system may also include a process controller in communication with the plurality of pumps for coordinating said mixing by the pumps.

In accordance with another aspect of the invention, red blood cell concentrate is mixed with an anti-pathogen solution to form an incubation solution.

BRIEF DESCRIPTION OF THE DRAWINGS

In the accompanying drawings:

FIG. 1A shows an exemplary blood processing system having a plurality of blood pumps in accordance with an embodiment of the present invention;

FIG. 1B shows an exemplary wiring diagram for one embodiment of the blood processing system shown inFIG. 1A;

FIG. 1C shows an exemplary wiring diagram for another embodiment of the blood processing system shown inFIG. 1A;

FIG. 2 shows an exemplary blood disposables set in accordance with an embodiment of the present invention;

FIG. 3A shows a front view of the pump cassette in accordance with an embodiment of the present invention;

FIG. 3B shows a rear view of the pump cassette in accordance with an embodiment of the present invention;

FIG. 4 shows a conceptual block diagram of the blood pump in accordance with an embodiment of the present invention;

FIG. 5A is an architectural flow diagram showing the relationship between the pneumatic control assembly and the other assemblies in accordance with an embodiment of the present invention;

FIG. 5B shows an exemplary embodiment of the pneumatic control assembly in accordance with an embodiment of the present invention;

FIG. 5C shows an exemplary embodiment of the air pump in accordance with an embodiment of the present invention;

FIG. 6A shows an exploded view of an exemplary front plate assembly in accordance with an embodiment of the present invention;

FIG. 6B shows a front view of an exemplary bezel in accordance with an embodiment of the present invention;

FIG. 6C shows a rear view of an exemplary bezel in accordance with an embodiment of the present invention;

FIG. 6D shows a front view of an exemplary bezel gasket in accordance with an embodiment of the present invention;

FIG. 6E shows a rear view of an exemplary bezel gasket in accordance with an embodiment of the present invention;

FIG. 7A shows an exploded view of the door assembly in accordance with an embodiment of the present invention;

FIG. 7B shows a front perspective view of the door assembly in accordance with an embodiment of the present invention;

FIG. 7C shows a rear perspective view of the door assembly in accordance with an embodiment of the present invention, in which the cassette receptacle is in a retracted position;

FIG. 7D shows a rear perspective view of the door assembly in accordance with an embodiment of the present invention, in which the cassette receptacle is in an open position;

FIG. 8 shows a side perspective view of the occluder assembly in accordance with an embodiment of the present invention;

FIG. 9 shows a cross-sectional view of an occluder in accordance with an embodiment of the present invention;

FIG. 10 shows an exploded view of the occluder assembly in accordance with an embodiment of the present invention;

FIG. 11 is a schematic diagram showing the pump cassette installed in the blood pump in accordance with an embodiment of the present invention;

FIG. 12 shows a process flow diagram describing the compounding and blood treatment process, which is coordinated by the process controller, in accordance with an embodiment of the present invention;

FIGS. 13A-B show a process flow diagram showing additional details of the blood processing operations in accordance with an embodiment of the present invention;

FIG. 14 shows a process flow diagram describing the blood pump dry CIT process in accordance with an embodiment of the present invention;

FIG. 15 shows a process flow diagram describing the blood pump working solution priming process in accordance with an embodiment of the present invention;

FIG. 16 shows a process flow diagram describing the blood pump wet CIT process in accordance with an embodiment of the present invention;

FIGS. 17A-D show a process flow diagram describing the blood mixing process in accordance with an embodiment of the present invention;

FIG. 18 shows a process flow diagram describing the volumetric calibration process in accordance with an embodiment of the present invention;

FIG. 19 shows a process flow diagram describing the process for manual blood pump teardown in accordance with an embodiment of the present invention; and

FIG. 20 shows a logic flow diagram showingexemplary logic2000 for mixing two liquids in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT

Embodiments of the present invention provide for safely and efficiently mixing two liquids. In order to mix two liquids, a first liquid is pumped into a first pump chamber of a pumping apparatus through a channel of the pumping apparatus. A second liquid is pumped from a second pump chamber of the pumping apparatus into either the channel or the first pump chamber, preferably while the first liquid is being pumped into the first pump chamber. In this way, the two liquids are mixed within the pumping apparatus, and, more specifically, within the channel and/or the first pump chamber of the pumping apparatus. The second liquid is preferably pumped in a pulsatile mode in which small quantities of the second liquid are pumped at intervals, for example, as described in U.S. Pat. No. 6,604,908, which is hereby incorporated herein by reference in its entirety. The quantity and/or the interval can be dynamically adjusted to result in a predetermined concentration of the two liquids. The contents of the first pump chamber are pumped to a receptacle.

FIG. 20 is a logic flow diagram showingexemplary logic2000 for mixing two liquids in accordance with an embodiment of the present invention. Beginning inblock2002, the logic pumps a first liquid into a first pump chamber of a pumping apparatus through a channel of the pumping apparatus, inblock2004. The logic pumps a second liquid from a second pump chamber of the pumping apparatus into one of the channel and the first pump chamber so as to mix the first liquid and the second liquid within the pumping apparatus, inblock2006. The logic dynamically adjusts the amount of second liquid pumped to obtain a predetermined concentration of first liquid and second liquid, in block2008. The logic pumps the contents of the first pump chamber into a receptacle, inblock2010. The various pumping and adjusting operations may be repeated as necessary to process a predetermined quantity of liquids. Thelogic2000 ends inblock2099.

In exemplary embodiments of the present invention, the pumping apparatus is a disposable pump cassette. The pump cassette typically includes two pump chambers and various valves. The pump chambers and valves are preferably operated pneumatically.

In exemplary embodiments of the present invention, an anti-pathogen solution is mixed with a red blood cell concentrate (RBCC) to form an incubation solution for reducing pathogens in the RBCC. The anti-pathogen solution is prepared by mixing a caustic anti-pathogen compound known as PEN110 or INACTINE, which is an organic solvent with a pH over 11 that is distributed by V.I. Technologies, Inc. of Watertown, Mass., with a buffer solution of sodium phosphate to a predetermined concentration (e.g., 1 part anti-pathogen compound to 99 parts buffer solution), preferably as described in Application D70. For convenience, this mixing of anti-pathogen compound with buffer solution may be referred to hereinafter as “compounding,” and an apparatus that performs such compounding may be referred to hereinafter as a “compounder” or “compounder pump.” The incubation solution is prepared by mixing the anti-pathogen solution with the RBCC to a predetermined concentration (e.g., 1 part anti-pathogen solution to 9 parts RBCC), as described below. For convenience, this mixing of anti-pathogen solution with RBCC may be referred to hereinafter as “blood processing,” and an apparatus that performs such blood processing may be referred to hereinafter as a “blood pump.”

System Overview

FIG. 1A shows an exemplaryblood processing system100 having a plurality of blood pumps in accordance with an embodiment of the present invention. Among other things, theblood processing system100 includes asingle compounder pump102 and ten essentially identical blood pumps104 organized as two banks of five blood pumps each. Thecompounder pump102 pumps buffer solution from abuffer solution container110 into a vial ofanti-pathogen compound108. The mixture, referred to as a working solution, is pumped into a workingsolution container112. Each of the blood pumps104 mixes working solution from the workingsolution container112 with red blood cell concentrate (RBCC) from aRBCC container106 to form an incubation solution that is pumped into anincubation bag118. The incubation solution is typically allowed to incubate for some period of time, after which it is rinsed to remove the anti-pathogen compound to produce a pathogen reduced blood product. Theblood processing system100 typically also includes twosterile docks114 that are used by the operator to splice together plastic tubing as necessary for various blood processing operations. Theblood processing system100 is controlled through auser interface116.

FIG. 1B shows an exemplary wiring diagram for one embodiment of theblood processing system100. Thecompounder pump102 and the blood pumps104 are typically powered from a common 12-Voltexternal power supply126, and are controlled by anexternal process controller120. Theprocess controller120 includes theuser interface116, acomputer122, and aserial port concentrator124. Thecompounder pump102 and the blood pumps104 are in communication with theprocess controller120 through theserial port concentrator124, for example, over RS-232 communication links. Theblood processing system100 typically includes atubing sealer130 for sealing plastic tubing as necessary for various blood processing operations. Theblood processing system100 typically includes an uninterruptible power supply (UPS)128 for maintaining electrical power to the 12-Volt power supply, the process controller, and other components in the event of a primary power loss.

FIG. 1C shows an exemplary wiring diagram for another embodiment of theblood processing system100. Theblood processing system100 may include a printer in communication with the process controller for printing out reports. Theblood processing system100 may include acard reader134 in communication with the process controller for card-based operator identification. Theblood processing system100 may include a wireless bar code scanner base station138 in communication with the process controller for receiving bar code information scanned using a wirelessbar code scanner136. Bar codes are typically used to track the various solution containers and the pumps on which those containers were processed.

Theprocess controller120 coordinates the actions of thecompounder pump102, the blood pumps104, and the operator throughout the various mixing operations, as described in greater detail in Application D72. Theprocess controller120 initiates high level embedded commands within the pumps to move and mix the fluids. Theprocess controller120 instructs the operator through the setup and teardown of each process through theuser interface116. Theuser interface116 is also used to inform the operator of any anomalies that may occur during mixing operations.

When theblood processing system100 is operating from theuninterruptible power supply128 and at other appropriate times, theprocess controller120 will prevent compounding and other pump operations from starting, although the pumps will generally be allowed to complete any ongoing operations. Furthermore, if the process controller fails, the pumps have internal logic for safely completing or terminating any ongoing operations.

Blood Disposables

In an exemplary embodiment of the present invention, theprocess controller120 coordinates blood processing for an entire bank of fiveblood pumps104 at a time. Specifically, five pump cassettes, each connected to a RBCC container and an incubation bag for receiving the incubation solution, are loaded respectively into the five blood pumps104. The five pump cassettes are preferably connected by a single working solution inlet tube to the working solution container so that all five blood pumps draw working solution from the single working solution container. For convenience, the five interconnected pump cassettes along with their respective incubation bags and various plastic tubing may be referred to hereinafter as a “blood disposables set.” The blood disposables set is preferably used for a single blood processing cycle and is then discarded. The blood disposables set is described in greater detail in Application D85.

FIG. 2 shows an exemplary blood disposables set200 in accordance with an embodiment of the present invention. The blood disposables set200 includes fivepump cassettes202_1-5, each respectively having aRBCC inlet tube204_1-5connected to an RBC inlet port of the pump cassette and an incubationsolution outlet tube206_1-5connected to an outlet port of the pump cassette and to an incubation-bag118_1-5. The blood disposables set200 also includes workingsolution distribution tubing212 that connects to a working solution inlet port on eachpump cassette202_1-5and to a single workingsolution inlet tube210 so that the working solution inlet ports of all pumpcassettes202_1-5are effectively connected to the single workingsolution inlet tube210. The workingsolution inlet tube210 preferably connects to the workingsolution distribution tubing212 close to where the working solution inlet port of themiddle pump cassette202₃connects to thetubing212, and the working solution inlet ports of each concentric pair of pump cassettes is preferably connected to the tubing212 a substantially equal distance from that center connection such that the working solution inlet ports of thepump cassettes202₁and202₅are essentially equidistant from the center connection and the working solution inlet ports of thepump cassettes202₂and202₄are essentially equidistant from the center connection. Among other things, this spacing of pump cassettes along thetubing212 facilitates priming of the pumps, as discussed below. In order to perform blood processing, eachRBCC inlet tube204 is connected to aseparate RBCC container106, and the workingsolution inlet tube210 is connected to the commonworking solution container112. The blood disposables set200 also includes six break-awayclosures214, one on each of theRBCC inlet tubes204 and one on the workingsolution inlet tube210. In order to reduce the likelihood of confusing which RBCC bag and which incubation bag is associated with each pump cassette, theRBCC inlet tubes204 and the incubationsolution outlet tubes206 are preferably coded, for example, by alternating between color-striped and clear tubing from cassette to cassette.

FIG. 3A shows a front view of thepump cassette202 in accordance with an embodiment of the present invention. Thepump cassette202 is essentially a rigid core including formations and sealingribs340 constituting various pumping chambers, fluid valves, and fluid pathways (channels). The rigid core is covered on each side by a flexible membrane (e.g., a flexible PVC sheet). The flexible membranes seal against the core and isolate theblood pump104 from fluids within the cassette. Thepump cassette202 is designed to interface with theblood pump104 in only one direction. For example, thepump cassette202 typically includes an asymmetric feature (such as the placement of tubing) that prevents the blood pump door from closing if thepump cassette202 is inserted incorrectly.

Among other things, thepump cassette202 includes a workingsolution inlet port304, anRBC inlet port305, avent port307, anoutlet port308 and two pumping chambers, namely a workingsolution chamber333 and anRBC chamber334. During blood processing, working solution from the workingsolution container112 is drawn into the workingsolution chamber333 through thetubing210 and212 and the workingsolution inlet port304, and is pumped from the workingsolution chamber333 into thechannel310 while RBCC from theRBCC container106 is drawn into theRBC chamber334 through theRBCC inlet tube204, theRBCC inlet port305, and thechannel310. This causes the working solution and RBCC to be mixed within thechannel310 and theRBC chamber334. The mixture (incubation solution) is pumped from theRBC chamber334 to theincubation bag118 through theoutlet port308 and the incubationsolution outlet tube206.

FIG. 3B shows a rear view of thepump cassette202 in accordance with an embodiment of the present invention. The rears view of thepump cassette202 shows various “volcano” valves that are used to open and close various fluid pathways within thepump cassette202. The valves include anRBC priming valve326, anRBC valve328, anincubation bag valve330, a workingsolution valve332, and a working solution connection toRBC line valve336. The volcano valves and the pumping chambers are all operated pneumatically from the rear of thepump cassette202, as discussed below.

Blood Pump

As discussed above, eachblood pump104 prepares incubation solution by mixing an anti-pathogen solution with RBCC. Adisposable pump cassette202 is used to handle the various fluids. Thepump cassette202 serves as an interface between theblood pump104, theRBCC container106, and theincubation bag118 so that no working solution, RBCC, or incubation solution comes into actual contact with the components of theblood pump104. Theblood pump104 preferably uses pneumatics to operate thepump cassette202 as well as other components, as discussed below.

Theblood pump104 produces the incubation solution by causing working solution to be drawn into the workingsolution chamber333 and pumping working solution from the workingsolution chamber333 into thechannel310 while drawing RBCC into theRBC chamber334 through thechannel310. This causes the working solution and RBCC to be mixed within thechannel310 and theRBC chamber334. The mixture (incubation solution) is pumped from theRBC chamber334 to theincubation bag118 through theoutlet port308.

In a typical embodiment of the present invention, the working solution is pumped from the workingsolution chamber333 using a pulsing technique in which small quantities of working solution are pumped at predetermined intervals and the pulsing of working solution is adjusted periodically using a closed feedback loop in order to produce an incubation solution having a predetermined concentration of working solution, with predetermined limits. Specifically, the working solution is delivered in a pulsatile mode where the pulse width of the exit valve on the working solution chamber is controlled. The fluid valve is pulsed at a pulse width and interval that is predetermined for each pumping stroke and is adjusted stroke-by-stroke according to the amounts of working solution and RBCC pumped, as described below. Theblood pump104 can support pulse widths above some minimum value, and the interval between pulses is increased in order to achieve an effective pulse width below the minimum value.

Theblood pump104 preferably includes a library of generic pump control (N-Pump) functions. The N-Pump library functions are used to perform various generic pumping operations such as, for example, pumping fluid into a chamber of the pump cassette, pumping fluid out of a chamber of the pump cassette, measuring the mount of fluid pumped, performing air detection, and maintaining tank pressures. Theblood pump104 preferably also includes a Fluid Logic Module (FLM) that contains higher level functions that employ the N-Pump library functions to implement application-specific functions (such as specific logic for mixing the working solution with the RBCC to produce the incubation solution).

Theblood pump104 includes one master board connected to two pump boards that together perform the N-Pump and FLM functions. The master board communicates to each of the pump boards via a multi-drop RS-485 bus. Each pump board controls a single pump chamber of thepump cassette202 and the valves on its board.

FIG. 4 shows a conceptual block diagram of theblood pump104 in accordance with an embodiment of the present invention. Among other things, theblood pump104 includes adoor assembly402, anoccluder assembly404, afront plate assembly408, apneumatic control assembly410, a power/communication interface412 including connectors for the 12-Volt power supply and the RS-232 communication link to theprocess controller120, andchassis components414. Each of these assemblies is discussed below.

Pneumatic Control Assembly

Thepneumatic control assembly410 provides positive and negative air pressure for operating the various other pneumatically controlled components and also acts as the general controller for theblood pump104. Thepneumatic control assembly410 contains three electromechanical pump module assemblies, namely a tank management module assembly and two chamber module assemblies (one for the working solution pump chamber and one for the RBC pump chamber). Each pump module assembly includes an aluminum manifold, pneumatic valves, pneumatic fittings, a valve interface board, and an electronics board that includes pressure transducers and a dedicated microprocessor. The tank management module assembly handles all communication between the blood pump and theprocess controller120, synchronizes pumping of the chamber module assemblies, maintains positive and negative air pressure in various accumulators, seals and unseals the door assembly, engages and disengages the occluders, monitors the door open/closed status, and monitors the air-in-line sensor, as described below. Each chamber management assembly controls a separate one of the pump chambers, and also controls the fluid valves associated with the pump chamber and measures the volume of liquids pumped through the pump chamber.

FIG. 5A is an architectural flow diagram showing the relationship between thepneumatic control assembly410 and the other assemblies in accordance with an embodiment of the present invention. In this figure, thepneumatic control assembly410 is represented bymaster module512,accumulator assembly513, workingsolution pump module514, andRBCC pump module515. Theair pump511 is considered to be one of thechassis components414. Theair pump511 generates high and low air pressure for themaster module512, which stores high and low air pressure in theaccumulator assembly513. Thepneumatic control assembly410 directs air pressure (positive and negative) to the various pneumatic mechanisms of the pump. Themaster module512 pneumatically controls bladders in theoccluder assembly404 and a bladder in thedoor assembly402, as discussed below. Themaster module512 provides high and low air pressure to the workingsolution pump module514 and theRBCC pump module515. The workingsolution pump module514 controls the workingsolution chamber333 and associated valves of thepump cassette202 through thefront plate assembly408, and theRBCC pump module515 controls theRBC chamber334 and associated valves of thepump cassette202 through thefront plate assembly408, as described below.

FIG. 5B shows an exemplary embodiment of thepneumatic control assembly410 in accordance with an embodiment of the present invention. Among other things, thepneumatic control assembly410 includes manifold mountingbracket502, a negative pressure accumulator (pressure bottle)513a, a positive pressure accumulator (pressure bottle)513b, a manualdoor vent mechanism503, the TankManagement Module Assembly512, the twoChamber Module Assemblies514 and515, and associated tubing and fittings.

Thetank management module512 includes an input/output (I/O) board, a CPU board, a valve-interface board, a pneumatic manifold system, pneumatic valves, pressure transducers 2-vent covers (mufflers), stand-offs, and associated tubing and fittings. Thetank management module512 is used to control the pressures in theaccumulators513, a bladder in thedoor assembly402, and bladders in theoccluder assembly404. The I/O board contains electrical controls for controlling LEDs that provide status information to the operator. The pressure transducers are used to monitor the pressures of theaccumulators513 and the bladder in thedoor assembly402.

In the un-powered state, the pneumatic valve that controls flow to the bladder in thedoor assembly402 preferably shuts closed. This prevents the door from being opened in the event of a loss of power.

In the un-powered state, the pneumatic valves that control flow to the bladders in theoccluder assembly404 are preferably channeled to vent. This causes the occluders to occlude the tubing to prevent further flow of fluid through the tubing, as discussed below.

Eachchamber module514 and515 includes a CPU board, a valve interface board, pneumatic manifold system, pneumatic valves (including a VSO (variable) valve), a VSX chamber (504 and505 respectively), O-ring, copper mesh, vent cover (muffler), stand-offs, pressure transducers, and associated tubing and fittings. Each chamber module assembly controls the pneumatics for one of the pumping chambers and its associated valves. TheVSX chambers504 and505 act as reference volumes in order to measure the volume of fluid that is delivered with the FMS system. The pressure transducers are used to monitor the pressure of the VSX chamber, and of the pumping chamber. The positive pneumatic system contains a pressure relief valve to prevent the air pump from pressurizing the positive system to greater than 16.0 psig.

In the un-powered state, all of the pneumatic valves preferably open the fluid valves to the positive pressure line. This ensures that the fluid valves are closed if there is a loss of power.

Theblood pump104 typically includes three microprocessor systems, one on thetank management module512 and one on each of thechamber modules514 and515. These three microprocessor systems monitor each other for normal operation. Each microprocessor system also monitors key internal processes and data for validity. If any of these monitors fail, a failsafe line permits any of the three processors to stop pumping operations, close all of the fluid valves and occluder, and send an anomaly signal to the process controller. If theblood pump104 detects an anomaly with the commands received from the process controller (e.g., commands received out of sequence), then theblood pump104 will stop fluid flow and send an anomaly signal to the process controller.

FIG. 5C shows an exemplary embodiment of theair pump511 in accordance with an embodiment of the present invention. Theair pump511 includes apump motor591 mounted to apump plate592 using double-sided tape594 and two miniature nylon cable ties595. Fourribbed isolator grommets593 are inserted into corresponding openings in thepump plate592.

Front Plate Assembly

Thefront plate assembly408 includes all necessary pneumatic pathways to interface to thedisposable pump cassette202. Thefront plate assembly408 includes a bezel and a bezel gasket through which thepump cassette202 is operated. During operation of theblood pump104, thepump cassette202 is positioned in thedoor assembly402 and is pressed against thefront plate assembly408 in alignment with the bezel and bezel gasket by a bladder in thedoor assembly402, as discussed below. Air lines connected to the bezel from thepneumatic control assembly410 are used to displace membranes of the bezel gasket to operate the various valves and chambers of thepump cassette202.

FIG. 6A shows an exploded view of an exemplaryfront plate assembly408 in accordance with an embodiment of the present invention. Among other things, thefront plate assembly408 includes a rigidfront plate602 to which are mounted abezel604,chamber foam606,spacer608, air-in-line sensor610,bezel gasket612,gasket retainer614,hardware616, dowel pins618, andgrommet620. Thebezel604,chamber foam606, andbezel gasket612 are mounted to thefront plate602 by thegasket retainer614 and associatedhardware616, forming a bezel assembly. This bezel assembly is used to control pumping and mixing of fluids using thepump cassette202, as described below. Thefront plate602 includes holes for allowing air tubes to pass between the rear of thebezel604 and thepneumatic control assembly410, which is typically situated behind thefront plate602. Thefront plate602 also includes openings for occluder blades and for engaging a door latch mechanism, as described below. The air-in-line sensor610 is positioned so as to align with and engage theRBCC inlet tube204, and is used during blood processing to detect air in theRBCC inlet tube204 indicating that there is no more RBCC to be processed.

FIG. 6B shows a front view of anexemplary bezel604 in accordance with an embodiment of the present invention. Thebezel604 is preferably a molded polycarbonate/ABS unit including, among other things, a workingsolution chamber cavity633 for operating the workingsolution chamber333 of thepump cassette202, anRBC chamber cavity634 for operating theRBC chamber334 of thepump cassette202, andvarious valve cavities635 for operating the various valves of thepump cassette202. Each of thechamber cavities633 and634 typically includes twoair holes638 through which air is pumped into and out of the chamber cavity. The workingsolution chamber cavity633 is preferably molded withrib structures636 that allow for airflow within the workingsolution chamber cavity633 but mechanically restrict the amount of working solution that can be drawn into the workingsolution chamber333 of thepump cassette202. The bezel with rib structures is described in greater detail in Application D75. Thecompounder102 preferably uses the same moldedbezel604 as theblood pump104, but with therib structures636 removed (e.g., by precision machining) to allow for greater pumping capacity.

FIG. 6C shows a rear view of thebezel604 in accordance with an embodiment of the present invention. Thebezel604 includes integral solvent bondable tubing connections (ports)637 to which pneumatic tubing from thepneumatic control assembly410 are connected. In this embodiment, each of thevalve cavities635 is associated with a singleintegral port637, and each of thechamber cavities633 and634 are associated with twointegral ports637. Theintegral ports637 allow the pneumatic connections to be made without independent fittings and accompanying O-rings.

FIG. 6D shows a front view of anexemplary bezel gasket612 in accordance with an embodiment of the present invention. Thebezel gasket612 fits over the front of thebezel604 and acts as an interface between thebezel604 and thepump cassette202 for sealing the fluid paths of thepump cassette202 and for actuating the chambers and valves of thepump cassette202. Thepump cassette202 is pressed firmly against the front side of thebezel gasket612 during blood processing in order to produce an air-tight seal between thebezel gasket612 and thepump cassette202. Thebezel gasket612 includes membranes that correspond to the chamber cavities and valve cavities. Positive and negative air pressure produced through the bezel cavities operate on the bezel gasket membranes, which in turn operate on the chambers and valves of thepump cassette202.

FIG. 6E shows a rear view of anexemplary bezel gasket612 in accordance with an embodiment of the present invention. The rear side of thebezel gasket612 contacts the front side of thebezel604, and is pressed firmly against thebezel604 during blood processing in order to produce an air-tight seal. Thebezel gasket612 includes membranes that correspond to the chamber cavities and valve cavities. Positive and negative air pressure produced through the bezel cavities operate on the bezel gasket membranes, which in turn operate on the chambers and valves of thepump cassette202.

Door Assembly

Thedoor assembly402 mounts to thefront plate assembly408, and provides a means to load and align thedisposable pump cassette202 within theblood pump104. Thedoor assembly402 provides a force on thepump cassette202 against the bezel assembly of thefront plate assembly408 in order to provide sealing of the cassette's fluid paths and valves, as described in greater detail in Application D73. Thedoor assembly402 includes a special latch system that helps maintain the seal, and also helps prevent accidental opening of the door during blood processing, as described in greater detail in Application D74. Thedoor assembly402 also provides a surface for the occluders to function against, as described below.

FIG. 7A shows an exploded view of thedoor assembly402 in accordance with an embodiment of the present invention. Among other things, thedoor assembly402 includes adoor cowl701, alatch spring post702, adoor latch703, acassette receptacle704, aback plate705, alatch pin706, abladder707 with an attachedpneumatic circuit730, aframe708, adoor pin709, adoor mounting bracket710, apiston assembly711 including apiston plate731 and apiston cover732, a humaninterface board assembly712, doublecoated tape713, aminiature cable tie714, recessedbumpers715,E-rings722,cable tie mount723, torsion springs724 and725,extension spring726, acassette orientation tab799, andvarious screws716,717,718,719,720, and721. The humaninterface board assembly712 is mounted to the inside of thedoor cowl701. Thepiston assembly711 includes arigid plate731 having a protrusion that is covered by thepiston cover732. Thebladder707, doublecoated tape713, andpiston assembly711 are sandwiched between theback plate705 and theframe708, which are mechanically coupled together to form aframe assembly750. Thedoor latch703 is positioned so that a handle portion is accessible from a front side of thedoor cowl701. Theframe assembly750 is mounted to the inside of thedoor cowl701 so that a latch portion of thedoor latch703 protrudes through theframe assembly750 and theframe assembly750 holds thedoor latch703 in place. Thecassette receptacle704 is pivotally mounted to theframe708 using thedoor mounting bracket710, thedoor pin709, and theE-rings722. Recessedbumpers715 reduce strain on the door if the door is opened too far or with excessive force. The torsion springs724 and725 aid the operator in closing the door, as the door has considerable weight due to the many components. Thecassette orientation tab799 prevents the door from being closed if the pump cassette is oriented incorrectly in thecassette receptacle704.

Thebladder707 is coupled to, and controlled by, apneumatic circuit730 that provides positive and/or negative air pressure to thebladder707. Positive pressure supplied to thebladder707 causes thebladder707 to expand in the direction of theframe708. This, in turn, causes theentire piston assembly711 to move toward thecontrol assembly408, such that thepiston cover732 presses against thepump cassette202 and/orcassette receptacle704, thereby producing an outward force on thedoor402 away from thecontrol assembly408. Alternatively, supplying negative pressure to thebladder707 causes thepiston assembly711 to move away from thepump cassette202 and/orcassette receptacle704, thereby reducing the outward force on thedoor402 away from thecontrol assembly408.

The door assembly is designed to permit single-handed operation, specifically by pulling up on the handle. However, thedoor latch703 is designed so that the door cannot be easily opened when the pump cassette is in place in thecassette receptacle704 with the door closed and thebladder707 is inflated. Specifically, the latch portions of thedoor latch703 have undercuts that are engaged by recesses in thefront plate assembly408. When the pump cassette is in place in thecassette receptacle704 with the door closed and thebladder707 is inflated so as to push the pump cassette against the bezel components of thefront plate assembly408, a sufficient force is generated between thedoor assembly402 and thefront plate assembly408 to prevent the door handle from being easily lifted. This door locking mechanism is described in greater detail in Application D74.

FIG. 7B shows a front perspective view of thedoor assembly402 in accordance with an embodiment of the present invention. The humaninterface board assembly712 having LEDs and the handle portion of thedoor latch703 are visible from the front of thedoor cowl701. A portion of thecassette receptacle704 and a portion of thepneumatic circuit730 are also visible.

FIG. 7C shows a rear perspective view of thedoor assembly402 in accordance with an embodiment of the present invention, in which thecassette receptacle704 is in a retracted position. Visible at the rear of thedoor cowl701 are theframe708, the latch portion of thedoor latch703, thecassette receptacle704, thepiston assembly711, thedoor mounting bracket710, the torsion springs724 and725, a portion of the humaninterface board assembly712, and a portion of thepneumatic circuit730.

FIG. 7D shows a rear perspective view of thedoor assembly402 in accordance with an embodiment of the present invention, in which thecassette receptacle704 is in an open position. Visible at the rear of thedoor cowl701 are theframe708, the latch portion of thedoor latch703, thecassette receptacle704, thepiston assembly711, thedoor mounting bracket710, the torsion springs724 and725, a portion of the humaninterface board assembly712, and a portion of thepneumatic circuit730.

Occluder Assembly

Theoccluder assembly404 mounts to the back of thefront plate assembly408, and is used to selectively occlude theRBCC inlet tube204, the incubationsolution outlet tube206, and the workingsolution distribution tube212 as needed for testing, blood processing, and protection in the event of a failure. In theblood pump104, theoccluder assembly404 includes two occluders, one operating on both theRBCC inlet tube204 and the incubationsolution outlet tube206, and the other operating on the workingsolution distribution tube212. The occluders are controlled pneumatically, and can be controlled independently.

In a typical embodiment of the present invention, each occluder includes an occluder blade that is operated by a flat spring and an inflatable bladder. The occluder blade is coupled to one end of the spring. When the bladder is deflated, the spring extends the occluder blade into an occluding position, which blocks the passage of fluid through the tube(s). When the bladder is inflated, the bladder bends the spring so as to retract the occluder blade from the occluding position, which enables the passage of fluid through the tube(s). In the event of a loss of pneumatics, the occluder defaults to the occluded position so as to prevent fluid from passing through the tubing.

FIG. 8 shows a side perspective view of theoccluder assembly404 in accordance with an embodiment of the present invention. Theoccluder assembly404 includes, among other things, a bottom housing801, atop housing802, a first occluder having anoccluder blade813 and other components operated pneumatically throughtube803, and a second occluder having anoccluder blade814 and other components operated pneumatically throughtube804. Theoccluder assembly404 is mounted to thefront plate assembly408, with theoccluder blades813 and814 protruding through slots in thefront plate assembly804. Thetubes803 and804 are connected to thepneumatic control assembly410.

FIG. 9 shows a cross-sectional view of an occluder in accordance with an embodiment of the present invention. Among other things, the occluder includes aflat occluder spring812 having a rear end coupled to thetop housing802 and a front end coupled to theoccluder blade814, abladder808 situated between thetop housing802 and thespring812, thetube804 coupled to thebladder808, and anadjuster810 for adjusting the protrusion of theoccluder blade814. When thebladder808 is inflated, theoccluder spring812 is deflected downward at the middle so as to shorten the effective length of theoccluder spring812 and retract theoccluder blade814. When thebladder808 is deflated, theoccluder spring812 extends flat and therefore extends theoccluder blade814. Theoccluder blade814 moves within guides (not shown) that allow the spring to extend and retract theoccluder blade814.

FIG. 10 shows an exploded view of theoccluder assembly404 in accordance with an embodiment of the present invention. Among other things, theoccluder assembly404 includesenclosure top802,enclosure bottom810, a first occluder including anoccluder blade813, ashaft821, afront bracket819, arear bracket817, abladder809, and atube803, and a second occluder including anoccluder blade814, ashaft820, afront bracket818, arear bracket816, abladder808, and atube804. Theoccluder blade813 mounts to thefront bracket819 via theshaft821, while theoccluder blade814 mounts to thefront bracket818 via theshaft820. Therear brackets816 and817 are mounted to theenclosure top802 viashaft825, blocks826 and827, and clamps828 and829. Therear brackets816 and817 are held in a substantially fixed position, although therear brackets816 and817 are able to rotate about theshaft825 as needed for operation of the occluders. Thefront bracket819 is mounted to theenclosure top802 viashaft821 and slidingblocks823 and824, while thefront bracket818 is mounted to theenclosure top802 viashaft820 and slidingblocks822 and823. Thefront brackets818 and819 are able to slide forward and backward along channels formed in the slidingblocks822,823, and824 as needed for operation of the occluders. Thus, theblocks826 and827 constrain the position of the occluder blades and act as bearing surfaces as the rear shaft rotates, and the slidingblocks822,823, and824 act as bearing surfaces for the front shafts as the occluder blades are actuated and released. It should be noted that the present invention is not limited to the block-type bearings shown, but rather various types of bushings, bearings, fixed blocks, moving blocks, or any combination thereof could be used to permit rotation of the rear shafts and/or brackets and translational movement of the front shafts. Theoccluder blades813 and814 can be manually retracted if necessary. The edge of theoccluder blades813 and814 that engages the tubing are typically rounded so as not to cut or crease the tubing.

Chassis Components

Thechassis components414 include various mechanical hardware components that are not considered part of the other assemblies. Among other things, thechassis components414 include theDC air pump511, a chassis base, a door sensor (and cable), mounting foot grommets, skins (housing), and associated hardware and fasteners. The housing includes a mounting point, on the back of the unit, for the manual piston bladder (door)vent503.

Pump Cassette Handling

FIG. 11 is a schematic diagram showing thepump cassette202 installed in theblood pump104 in accordance with an embodiment of the present invention. Thepump cassette202 is installed in thecassette receptacle704. Thedoor assembly402 will only close if thepump cassette202 is oriented correctly in thecassette receptacle704, and will not close if thepump cassette202 is inserted backwards so that the tubing connected to thepump cassette202 does not align with corresponding channels in thedoor latch703. When thedoor assembly402 is closed and the bladder in thedoor assembly402 is inflated, thepump cassette202 is pressed tightly against thebezel gasket612 andgasket retainer614 on thefront panel assembly408, theRBCC inlet tube204 is captured by the air-in-line sensor610 on thefront plate assembly408, theoccluder blade813 aligns with and occludes the workingsolution distribution tube212, and theoccluder blade814 aligns with and occludes both theRBCC inlet tube204 and the incubationsolution outlet tube206.

Blood Processing

As discussed above, thecompounder102 and the blood pumps104 operate under control of theprocess controller120. In exemplary embodiments of the present invention, introduction of the anti-pathogen compound into the RBCC is performed in two stages, a first stage in which the anti-pathogen compound is mixed with buffer solution to a first concentration to form the working solution, and a second stage in which the working solution is mixed with the RBCC to a second concentration to form the incubation solution. The two-stage process is described in more detail in Application D72.

FIG. 12 shows a process flow diagram describing the compounding and blood treatment process, which is coordinated by theprocess controller120, in accordance with an embodiment of the present invention. Rectangular blocks indicate commands sent to the pump by theprocess controller120. Rounded blocks indicate instructions sent to the operator by theprocess control120.

The process starts inblock1201. Inblock1202, the process controller instructs the operator to load and scan a compounder disposable set. After the compounder disposable set is loaded into the compounder, the process controller instructs the compounder to run a dry cassette integrity test (CIT) inblock1203. Assuming the dry CIT is acceptable, the process controller instructs the operator to hang, scan, and connect the buffer solution bag so that the buffer solution bag is connected to the inlet port of the pump cassette, inblock1204. The process controller then instructs the compounder to prime the compounder disposable set, inblock1205. The process controller then instructs the compounder to run a wet CIT, inblock1206. Assuming the wet CIT is acceptable, the process controller then instructs the operator to scan and load the vial assembly and spike receptacle into the vial spike assembly, inblock1207. The process controller then instructs the compounder to spike the vial, inblock1208. Once spiking is completed, the process controller instructs the compounder to perform the compounding operation, inblock1209. Compounding is described in more detail in Application D70.

After compounding is complete, the process controller coordinates “teardown” of the compounder for removal and disposal of the compounder disposable set from the compounder. Specifically, with reference again toFIG. 12, the process controller instructs the operator to heat seal the working solution line, inblock1235, and then agitate and invert the working solution bag, inblock1214. The process controller then instructs the operator to heat seal the buffer solution line, inblock1227. The process controller then instructs the operator to clamp the lines leading to the vial, inblock1228. The process controller then instructs the compounder to release the compounder door, inblock1231, which is accomplished by deflating the bladder in the door assembly. The process controller then instructs the compounder to release the bladder pressure on the vial spike (piston), inblock1232. The process controller then instructs the operator to remove the compounder disposables from thecompounder1233.

After compounder “teardown” is complete, the process controller coordinates the blood processing operations in which the RBCC is mixed with working solution by the blood pumps104 in order to produce the incubation solutions. Specifically, inblock1210, theprocess controller120 instructs the operator to load and scan a blood disposables set in one of the banks of blood pumps104. Theprocess controller120 may instruct the operator to scan, for each blood pump, theRBCC bag106, theblood pump104, and theincubation bag118. Theprocess controller120 stores this information so that there is a correlation between eachblood pump104 and the solutions processed and produced by it. This information can be used, for example, to identify all incubation solutions produced by aparticular blood pump104 if theblood pump104 is found to be defective.

After the blood disposables set is loaded, theprocess controller120 instructs the blood pumps120 to perform a dry CIT, inblock1212. The dry CIT operation is described in more detail with reference toFIG. 14 below. Assuming the dry CIT is successful, theprocess controller120 then instructs the operator to connect the workingsolution inlet tube210 of the blood disposables set to the workingsolution bag112 using thesterile dock114, inblock1213, and open the break-away closure on the workingsolution inlet tube210, inblock1215. Theprocess controller120 then coordinates working solution priming of the blood pumps104, inblock1216, and then performs a wet CIT on each of the blood pumps104, inblock1217. The priming and wet CIT operations are described in more detail respectively with reference toFIGS. 15 and 16 below. Assuming the wet CIT is successful, theprocess controller120 instructs the operator to open the break-away closures on theRBCC inlet tubes204, inblock1218. These break-away closures are not opened earlier in order to prevent contamination of the blood in case of a blood pump failure.

After the break-away closures are opened, theprocess controller120 instructs the blood pumps104 to mix the RBCC with the working solution to produce the incubation solutions, inblock1219. The blood mixing operation is described in more detail with reference toFIG. 17 below.

After blood mixing is complete, theprocess controller120 instructs the operator to heat seal the incubationsolution outlet tubes206, inblock1220, and to heat seal the workingsolution distribution tubes212, inblock1221. Theprocess controller120 then instructs the blood pumps104 to test the heat seal on the incubationsolution outlet tubes206, inblock1223. Assuming the tubes are sealed, theprocess controller120 instructs the blood pumps104 to release their respective doors, inblock1224. Theprocess controller120 then instructs the operator to remove theincubation bags118, inblock1225, and to tear down the blood disposables set, inblock1226.

If there is enough working solution remaining for another blood processing cycle, then the process may recycle to block1210 to coordinate blood processing operations for another bank of blood pumps. If and when the working solution has expired or there is not enough working solution remaining for another blood processing cycle, then the process controller typically instructs the operator to remove the working solution bag, inblock1236. The process ends inblock1234.

FIGS. 13A-B show a process flow diagram showing additional details of the blood processing operations in accordance with an embodiment of the present invention. The process begins inblock1301. A check is first made to confirm that the bank of blood pumps104 is configured properly, inblock1302. This involves, among other things, confirming that there is communication between theprocess controller120 and the fiveblood pumps104, confirming that all fiveblood pumps104 are configured to operate as blood pumps, and confirming that all fiveblood pumps104 contain the correct version of embedded software. The process enters anomaly handling, inblock1303, if the bank is not configured properly.

If the bank is configured properly, then a determination is made as to whether there is a sufficient quantity of working solution and a sufficient amount of time for performing the blood processing operation, inblock1304. If there is no working solution, then the compounder setup and process operation is performed as described in Application D70, inblock1308. If there is an insufficient amount of working solution, then the compounder teardown operation is performed as described in Application D70, inblock1305, and, inblock1306, the operator is given the option to either terminate the blood processing operation, in which case the process ends inblock1333, or continue the blood processing operation, in which case the compounder setup and process operation is performed as described in Application D70, inblock1308.

If there is a sufficient quantity of working solution inblock1304, or after working solution is prepared inblock1308, the blood disposables set is loaded into the blood pumps104. If the occluders are engaged, inblock1309, then the door is unsealed, inblock1310. Once the door is unsealed, the operator is instructed to load the blood disposables set, inblock1311, and to close the door. When the door is confirmed to be closed, inblock1314, the operator is instructed to scan the RBCC bags, blood pumps, and incubation solution bags, inblock1313. When scanning is complete, inblock1314, the blood pumps104 are instructed to seal their respective doors, inblock1315. If a door is unable to be sealed, then the process enters anomaly handling, inblock1316, which typically includes instructing the operator to reload the pump cassette. If the door is able to be sealed, then the blood pumps104 are instructed to perform the dry CIT, inblock1317. If the dry CIT fails, then the process enters anomaly handling, inblock1318, which typically involves instructing the operator to reload the pump cassette and running the dry CIT again. If the dry CIT passes, then the operator is instructed to connect the workingsolution inlet tube210 to the workingsolution bag112 using the sterile dock and to open the break-away closure on the working solution line, inblock1319. The blood pumps104 are then instructed to perform the priming process, inblock1320. If the priming process fails, then the process enters anomaly handling, inblock1320. If priming is successful, then the blood pumps104 are instructed to perform the wet CIT, inblock1322. If the wet CIT fails, then the process enters anomaly handling, inblock1323. If the wet CIT passes, then the operator is instructed to open the break-away closures on the RBCC inlet tubes, inblock1324. The blood pumps104 are then instructed to mix the RBCC and the working solution to form incubation solution, inblock1325. If there is a failure during mixing, then the process enters anomaly handling, inblock1326.

Assuming blood processing is successful, the operator is instructed to heat seal the incubation and working solution lines, inblock1327. Theblood units104 are then instructed to test the seal on the incubation line, inblock1328. If the test fails, then the process enters anomaly handling, inblock1329.

Assuming the incubation line is sealed, then the blood pumps104 are instructed to release their respective doors, inblock1330, after which the operator is instructed to teardown the blood disposables set, inblock1331. A closed-case file is prepared, inblock1332. The process ends inblock1333.

Blood Pump Dry Cassette Integrity Test

The dry cassette integrity test (CIT) is used to identify air leaks in the cassette membranes prior to pumping any fluids. Identifying a cassette with a membrane hole will protect the RBCC from being contaminated by a potentially non-sterile cassette, and will reduce the potential of pumping fluid into the blood unit itself. Also, at the time of the dry CIT, an internal pressure transducer calibration check is performed in order to ensure that none of the transducers have failed or drifted out of calibration. Also during the dry CIT, the fluid valve leading to the air vent on the cassette is tested by closing the valve, pressurizing the pump chamber, and observing the pressure decay.

FIG. 14 shows a process flow diagram describing the blood pump dry CIT process in accordance with an embodiment of the present invention. The dry CIT process begins inblock1401. The positive pneumatic system is first isolated from the cassette and a baseline leak rate for the positive assembly is obtained, specifically by closing the workingsolution line occluder813, inblock1402, opening all fluid valves and closing the variable valves, inblock1403, measuring the positive tank leak rate, inblock1404, and generating an error signal if the positive tank leak rate is greater than or equal to the predetermined threshold, inblock1405.

Then, the negative pneumatic system is isolated from the cassette and a baseline leak rate for the negative assembly is obtained, specifically by closing all fluid valves, inblock1407, measuring the positive tank leak rate, inblock1408, and generating an error signal if the negative tank leak rate is greater than or equal to a predetermined threshold, inblock1409.

Then, the process tests the cassette sheeting of the valves outside of the volcano valves, specifically by opening the workingsolution line occluder813, inblock1410, measuring the positive tank leak rate, inblock1411, and generating an error signal if the positive tank leak rate is greater than or equal to a predetermined threshold, inblock1412.

Then, the process tests the cassette sheeting at the center of the volcano valves, specifically by opening valves1A1 and2A1 and all fluid valves, inblock1413, measuring the positive and negative tank leak rates, inblock1414, and generating an error signal if the positive or negative tank leak rate is greater than or equal to a predetermined threshold, inblock1415.

Then, the process verifies calibration of the positive transducers, specifically by isolating the positive transducers and connecting the positive transducers together, inblock1416, measuring the positive tank leak rate, inblock1417, generating an error signal if the positive tank leak rate is greater than or equal to a predetermined threshold, inblock1418, determining whether all positive transducers agree to within a predetermined threshold, inblock1419, and generating an error signal if the positive transducers do not agree to within a predetermined threshold, inblock1420.

Then, the process verifies calibration of the negative transducers, specifically by isolating the negative transducers and connecting the negative transducers together, inblock1421, measuring the negative tank leak rate, inblock1422, generating an error signal if the negative tank leak rate is greater than or equal to a predetermined threshold, inblock1423, determining whether all negative transducers agree to within a predetermined threshold, inblock1424, and generating an error signal if the negative transducers do not agree to within a predetermined threshold, inblock1425.

Finally, the process tests integrity of the fluid valve leading to the vent filter, specifically by filling the chamber, inblock1426, pressurizing the chamber, inblock1427, measuring the chamber leak rate, inblock1428, and generating an error signal if the chamber leak rate is greater than or equal a predetermined threshold, inblock1429. The dry CIT process ends inblock1430.

Blood Pump Priming

The working solution priming process operates on an entire bank of five blood pumps, where all blood pumps share a single working solution line. The working solution priming process is coordinated by theprocess controller120 so as to prevent one pump from drawing in air that is being expelled by another pump, specifically by priming the operating the blood pumps symmetrically from the middle blood pump outward. Each blood pump is responsible for detecting “no flow” conditions during priming and also for detecting air in the working solution chamber of thepump cassette202 after the priming operation is complete. The priming process uses two operations, namely a “put” operation and a “get” operation. The “put” operation involves pumping the contents of the working solution chamber of the pump cassette202 (air and/or working solution) out through the workingsolution inlet304 to the working solution bag, specifically by applying a positive pressure to the working solution chamber. The “get” operation involves drawing from the workingsolution inlet304, specifically by applying a negative pressure to the working solution chamber. For convenience, the fiveblood pumps104 in a bank are referred to numerically from one to five, where pump three is the middle pump of the bank, pumps two and four are the pumps adjacent to the middle pump, and pumps one and five are the outside pumps.

FIG. 15 shows a process flow diagram describing the blood pump working solution priming process in accordance with an embodiment of the present invention. The priming process begins inblock1501. Inblock1502, a put operation is performed on all five blood pumps. This removes as much air as possible from the working solution chambers of thepump cassettes102. Then, get operations are performed on the blood pumps, starting with pump three, inblock1503, then pumps two and four simultaneously, inblock1504, and then pumps one and five simultaneously, inblock1505. Then, put operations are performed on the blood pumps, starting with pump three, inblock1506, then pumps two and four simultaneously, inblock1507, and then pumps one and five simultaneously, inblock1508. Then, get operations are performed on the blood pumps, starting with pump three, inblock1509, then pumps two and four simultaneously, inblock1510, and then pumps one and five simultaneously, inblock1511. Then, put operations are performed on the blood pumps, starting with pump three, inblock1512, then pumps two and four simultaneously, inblock1513, and then pumps one and five simultaneously, inblock1514. Finally, get operations are performed on all five pumps simultaneously, inblock1518. If a blood pump detects a “no flow” condition during any of the get and put operations, an error condition is raised inblock1516, and priming is terminated. If a blood pump detects air in the working solution chamber after completion of the priming process, then an error condition is raised inblock1517. The priming process ends inblock1518.

Blood Pump Wet Cassette Integrity Test

The wet cassette integrity test (CIT) is used to identify defects within the injection-molded body of the cassette. The wet CIT involves testing the functionality of all of the fluid valves within the cassette as well as testing for “cross-talk” between the fluid paths and fluid pump chambers within the cassette. The wet CIT is performed on a partially primed cassette, after priming the working solution pump chamber, but before priming the RBC pump chamber. Therefore, a complete wet CIT is performed on the working solution pump chamber, but the RBC pump chamber is tested using air pressure and decay. Priming and wet testing of the RBC pump chamber is performed during blood mixing, as discussed below.

FIG. 16 shows a process flow diagram describing the blood pump wet CIT process in accordance with an embodiment of the present invention. The wet CIT process begins inblock1601, and involves three passes ofblocks1602 through1619. In each pass, the workingsolution line occluder813 is retracted, inblock1602, and various measurements are performed on both chambers, inblock1603. If the measurements are outside of a predetermined threshold (NO in block1604), then an error signal is generated, inblock1605. Otherwise, a chamber filling operation is performed, inblock1606. During the first pass, both chambers are filled; during the second pass, only one chamber is filled; during the third pass, only the other chamber is filled. After the chamber filling operation, various measurements are performed on the chambers, inblock1607. If the measurements are outside of a predetermined threshold (NO in block1608), then an error signal is generated, inblock1609. At this point, the workingsolution line occluder813 is left retracted during the first pass, but is closed during the second and third passes, inblocks1610 and1611. The required fluid valves are then opened, inblock1612, tank pressure is applied to the chambers for a predetermined amount of time, inblock1613, and various measurements are performed on the chambers, inblock1614. If the measurements are outside of a predetermined threshold (NO in block1615), then an error signal is generated inblock1616. Otherwise, the process determines whether the volume displaced is within some threshold, inblock1617. If not, then an error signal is generated, inblock1618. After all three passes are complete, the workingsolution line occluder813 is opened, inblock1620, and both chambers are purged to the working solution bag, in block1621. The process ends inblock1622.

Blood Mixing

The blood mixing process is performed essentially in three stages, namely a priming stage, a mixing stage, and a residuals stage. The priming stage involves priming theRBC pump chamber334 from theRBCC bag106. The mixing stage involves repetitively drawing a quantity of working solution in to the workingsolution pump chamber333 and drawing a quantity of RBCC through thechannel310 into theRBC pump chamber334 while pulsing working solution from the workingsolution pump chamber333 into thechannel310 so that the working solution and RBCC mix within thechannel310 and theRBC pump chamber334. The pulsing of working solution is dynamically adjusted so that the resulting incubation solution has a predetermined concentration of working solution, within certain limits. The mixing stage continues until air is detected in theRBCC inlet tube204 by the air-in-line sensor610, signaling that there is no more RBCC to be processed. The residuals stage handles the residual contents in the RBC pump chamber334 (if any) following the mixing stage. In the residuals stage, the concentration of working solution and RBCC in theRBC pump chamber334 is measured, and the contents of theRBC pump chamber334 are delivered to theincubation bag118 if and only if the concentration of working solution and RBCC is within a predetermined specification. The overall concentration of working solution in the incubation solution is also measured, and a signal is generated to indicate whether or not the incubation solution is usable. The blood mixing process preferably prevents fluid from being pushed back into the working solution line after RBCC has been introduced into the pump cassette in order to prevent contamination of the working solution.

FIGS. 17A-D show a process flow diagram describing the blood mixing process in accordance with an embodiment of the present invention. The process begins inblock1701, and proceeds to prime theRBC pump chamber334. Specifically, theRBC occluder814 is opened, inblock1702, and the contents of theRBC pump chamber334 are purged to theRBCC bag106, inblock1703. If a no flow condition is detected inblock1704, then the process ends in failure inblock1705. Otherwise, theRBC pump chamber334 is filled from theRBCC bag106, inblock1706. If a no flow condition is detected inblock1707, then the process ends in failure inblock1705. Otherwise, the contents of theRBC pump chamber334 is purged back to theRBCC bag106, inblock1708, and the volume of theRBC pump chamber334 is computed, inblock1709. If a no flow condition is detected inblock1710, then the process ends in failure inblock1705. If air is detected in theRBC pump chamber334 inblock1711, then an error signal is generated, inblock1712, and a second attempt is made to prime theRBC pump chamber334 by repeatingblocks1706 through1711. If air is again detected in theRBC pump chamber334 inblock1711, then the process ends in failure inblock1713.

If theRBC pump chamber334 is successfully primed, then the process continues with the mixing stage. Specifically, the workingsolution pump chamber333 is filled from the workingsolution bag112 with working solution, inblock1714. The volume of the workingsolution pump chamber333 is measured, inblock1715. If air is detected in the workingsolution pump chamber333 inblock1716, then the process ends in failure inblock1717. If a no flow condition is detected inblock1718, then the process ends in failure inblock1719.

The RBCC is then mixed with working solution, inblock1720, specifically by drawing RBCC from theRBCC bag106 through thechannel310 into theRBC pump chamber334 while simultaneously pulsing working solution from the workingsolution pump chamber333 into thechannel310 so that the working solution and RBCC are mixed within thechannel310 and theRBC pump chamber334. While this mixing is being performed, the process is monitoring for air in theRBCC inlet tube204, inblock1742. Assuming no air is detected in theRBCC inlet tube204, inblock1742, the volumes of bothchambers333 and334 are measured, inblock1721. If air is detected in theRBC pump chamber334 inblock1722, then the process ends in failure inblock1723. If a no flow condition is detected inblock1724, then the process ends in failure inblock1725.

After mixing the working solution and RBCC, the concentration of working solution to RBCC in theRBC pump chamber334 is calculated, inblock1726, and a determination is made whether the concentration for this particular chamber is within predetermined specifications, inblock1727. If the concentration of working solution to RBCC in theRBC pump chamber334 is outside of specifications, then an error condition is signaled, inblock1728. In any case, though, the pulse width is adjusted based upon the concentration of working solution to RBCC in theRBC pump chamber334, inblock1729, and the contents of theRBC pump chamber334 are delivered to theincubation bag118, inblock1730. The volume of theRBC pump chamber1731 is measured, inblock1731. If a no flow condition is detected inblock1732, then the process ends in failure inblock1733.

In this first pass of the mixing stage, fromblock1734, theRBC pump chamber334 is filled from theRBCC bag106, inblock1735. If a no flow condition is detected inblock1736 while attempting to fill theRBC pump chamber334 from theRBCC bag106 then the process ends in failure inblock1737. Otherwise, the contents of theRBC pump chamber334 are purged to theRBCC bag106, inblock1738, and the volume of theRBC pump chamber334 is computed, inblock1739. If a no flow condition is detected inblock1740 while attempting to purge the contents of theRBC pump chamber334, then the process ends in failure inblock1741. Otherwise, the mixing stage continues by recycling to block1714 and repeatingblocks1714 through1734. During the second and subsequent passes of the mixing stage, the process recycles fromblock1734 to block1714, omittingblocks1735 through1741.

When air is detected in theRBCC inlet tube204, inblock1742, filling of theRBC pump chamber334 with RBCC and working solution is aborted (preferably before air has entered the RBC pump chamber), inblock1743, and a volume calculation is performed for both chambers, inblock1744. If air is detected in theRBC pump chamber334 inblock1745, then the process ends in failure inblock1746. Assuming that there is no air in theRBC pump chamber334, then the concentration of working solution to RBCC in theRBC pump chamber334 is calculated, inblock1747, and a determination is made whether the concentration for this particular chamber is within predetermined specifications, inblock1748. If and only if the concentration of working solution to RBCC in theRBC pump chamber334 is within specifications, the contents of theRBC pump chamber334 are delivered to theincubation bag118, inblock1749, theRBC pump chamber334 is filled from theRBCC bag106, inblock1750, and, upon detecting air in theRBC pump chamber334 inblock1751, the contents of theRBC pump chamber334 are delivered to theincubation bag118, inblock1752. Whether or not the residual contents of theRBC pump chamber334 are delivered to theincubation bag118, the overall concentration of working solution to RBCC in the incubation solution is calculated, inblock1753. If the overall concentration is outside of specifications, then an error condition is signaled, inblock1755. In any case, process data is sent to theprocess controller120, inblock1754. The process ends inblock1755.

Manual Teardown

During normal blood pump teardown, theblood pump104 receives commands from theprocess controller120 to release pressure against the pump door so that the door can be opened by the operator. The pressure against the door comes from both the door piston bladder and the occluders. While the door piston bladder is pressurized and the tubing occluders are engaged, it is virtually impossible for the operator to open the pump door and remove the pump cassette. If communication between theprocess controller120 and theblood pump104 is lost, then the operator will need to relieve this pressure manually in order to remove the cassette. Among other things, this involves the operator pressing the manual door release valve on the back of the pump to deflate the bladder in the door assembly. The operator may also manually retract the occluders if necessary.

FIG. 19 shows a process flow diagram describing the process for manual blood pump teardown in accordance with an embodiment of the present invention. The process starts inblock1901. The operator is instructed to heat seal the incubation and working solution lines, inblock1902. Theblood pump104 is then instructed to test the heat seal of the incubation line, inblock1903. If the incubation line is not sealed, then the process enters anomaly handling, inblock1904. Assuming the incubation line is sealed, then theblood pump104 is instructed to test the heat seal of the working solution line, inblock1905. If the working solution line is not sealed, then the process enters anomaly handling, inblock1906. Theblood pump104 is instructed to release the door, inblock1907, and the operator is instructed to press the manual door release valve on the back of the pump to deflate the bladder in the door assembly, inblock1908, if theblood pump104 does not release the door. The operator then manually retracts the occulders if necessary to allow opening of the door, inblock1909. The operator then removes the blood disposables, inblock1910. A close-case file is created indicating the failure, inblock1911. The process ends inblock1912.

Volumetric Calibration

Theblood pump104 is typically calibrated periodically to verify its ability to accurately measure volumes of pumped fluids. In exemplary embodiments of the invention, this calibration is done by running test measurements with two different test cassettes having different but known chamber volumes.

FIG. 18 shows a process flow diagram describing the volumetric calibration process in accordance with an embodiment of the present invention. The process begins inblock1801. The operator is instructed to scan a bar code on theblood pump104 inblock1802 in order to test theblood pump104. The operator is then instructed to load the first test cassette, inblock1803. Upon confirmation that the door is closed, inblock1804, the door is sealed, inblock1805. If the door fails to seal properly, then the process enters anomaly handling, inblock1806. If the door seals properly, a dry CIT is run, inblock1807. If the dry CIT fails, then the process enters anomaly handling, inblock1808. If the dry CIT passes, then a volume calibration test is run to measure the volume of the chambers, inblock1809. If the difference between the measured volume and the known volume of the first cassette is greater than or equal to some predetermined threshold, then the process enters anomaly handling, inblock1810. Otherwise, the door is released, inblock1811, and the operator is instructed to load the second test cassette, inblock1812. Upon confirmation that the door is closed, inblock1813, the door is sealed, inblock1814. If the door fails to seal properly, then the process enters anomaly handling, inblock1815. If the door seals properly, a dry CIT is run, inblock1816. If the dry CIT fails, then the process enters anomaly handing; inblock1817. If the dry CIT passes, then a volume calibration test is run to measure the volume of the chambers, inblock1818. If the difference between the measured volume and the known volume of the second cassette is greater than or equal to some predetermined threshold, then the process enters anomaly handling, inblock1819. Otherwise, a test pass determination is made, inblock1820, and a report is printed, inblock1821. The door is released, inblock1822, and the operator is instructed to remove the second test cassette, inblock1823. The process ends inblock1824.

It should also be noted that the flow diagrams are used herein to demonstrate various aspects of the invention, and should not be construed to limit the present invention to any particular flow or implementation. In some cases, certain process steps can be omitted or performed in a different order than shown without changing the overall results or otherwise departing from the true scope of the invention.

The present invention may be embodied in other specific forms without departing from the true scope of the invention. The described embodiments are to be considered in all respects only as illustrative and not restrictive.

Claims (11)

What is claimed is:

1. A method for mixing a first liquid with a second liquid, the method comprising:

actuating a first pump chamber of a membrane pumping apparatus by applying fluid pressure to the membrane to pump a first liquid into the first pump chamber through a channel of the membrane pumping apparatus; and

actuating a second pump chamber of the membrane pumping apparatus by applying fluid pressure to the membrane to pump a quantity of a second liquid from the second pump chamber into one of the channel and the first pump chamber so as to mix the first liquid and the second liquid within the first pump chamber.

2. A method according toclaim 1, wherein the second pump chamber is actuated by applying fluid pressure to the membrane to pump the second liquid into one of the channel and the first pump chamber during said pumping of the first liquid.

3. A method according toclaim 1, wherein the membrane pumping apparatus is a pump cassette having pneumatically operated first and second pump chambers and a plurality of pneumatically operated valves, and wherein actuating the first and second pump chambers comprising:

pneumatically operating the pump chambers and the valves.

4. A method according toclaim 1, wherein actuating the second pump chamber to pump the quantity of the second liquid comprising:

actuating the second pump chamber by applying fluid pressure to the membrane in a pulsatile mode.

5. A method according toclaim 4, wherein the pulsatile mode is characterized by a pulse width and pulse interval, and wherein the method further comprising:

determining a concentration of first liquid and second liquid in the first pump chamber; and

dynamically adjusting at least one of the pulse width and pulse interval based on the concentration of first liquid and second liquid in the first pump chamber.

6. A method according toclaim 5, further comprising:

actuating the second pump chamber by applying fluid pressure to the membrane to pump a second quantity of the second liquid from the second pump chamber into one of the channel and the first pump chamber using at least one of the dynamically adjusted pulse width and the dynamically adjusted pulse interval.

7. A method according toclaim 1, further comprising:

actuating the first pump chamber by applying fluid pressure to the membrane to pump the contents of the first pump chamber to a receptacle.

8. A method according toclaim 7, wherein the receptacle is external to the membrane pumping apparatus.

9. A method according toclaim 1, wherein the first pump chamber receives the first liquid from a first liquid container external to the membrane pumping apparatus.

10. A method according toclaim 1, further comprising:

prior to actuating the second pump chamber by applying fluid pressure to the membrane to pump the quantity of the second liquid from the second pump chamber, actuating the second pump chamber by applying fluid pressure to the membrane to pump second liquid into the second pump chamber from a second liquid container.

11. A method according toclaim 10, wherein the second liquid container is external to the membrane pumping apparatus.

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